The three major classes of herpes simplex virus genes are transcribed by RNAP II. Each class is regulated in a distinct manner, having unique requirements for the initiation of transcription. In a lytic infection, the first set of genes to be expressed, the IE genes, are regulated by the assembly of a multiprotein enhancer complex which is dependent upon the interaction of viral (aTIF) and cellular Oct-1, C1 factor) transcription factors. Previously, cDNAs encoding the unique cellular C1 factor were isolated and characterized. Expression and purification of this factor have allowed for the delineation of small domains of the polypeptide which are responsible for the direct recognition of the viral aTIF and the cellular homeodomain protein, Oct-1. As the C1 factor was shown to be highly conserved across species, two animal model systems are being developed for the analysis of the role of this factor in both viral and cellular gene expression. As the mouse is the primary model for the lytic/latent cycle of herpes simplex virus, cDNA and genomic clones have been isolated which encode the highly related homologue. The development of transgenic animals will provide a genetic basis for the role of this protein in the regulation of hsv IE gene expression in both a lytic and reactivated infection. Similarly, drosophila cells also contain a functional homologue of the C1 factor. This protein has been biochemically purified and shown to exhibit many of the physical characteristics of the mammalian protein. The isolation of the gene encoding this factor will allow for the development of mutants which should provide an accessible genetic system for the role of the factor in basic cellular processes.